REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Human TruStain FcX	Biolegend	cat # 422302; RRID: AB_2818986
Anti-Human CCR4 (L291H4) BV421	Biolegend	cat # 359414; RRID: AB_2562435
Anti-Human CCR6 (G034E3) BV650	Biolegend	cat # 353426; RRID: AB_2563869
Anti-Human CCR7 (G043H7) PE-Dazzle594	Biolegend	cat # 353236; RRID: AB_2563641
Anti-Human CD127 (A019D5) BV605	Biolegend	cat # 351334; RRID: AB_2562022
Anti-Human CD19 (HIB19) BV605	Biolegend	cat # 302244; RRID: AB_2562015
Anti-Human CD19 (HIB19) BV650	Biolegend	cat # 302238; RRID: AB_2562097
Anti-Human CD19 (HIB19) PE	Biolegend	cat # 302208; RRID: AB_314238
Anti-Human CD25 (BC96) APC-Cy7	Biolegend	cat # 302614; RRID: AB_314284
Anti-Human CD27 (O323) PE-Cy7	Biolegend	cat # 302838; RRID: AB_2561919
Anti-Human CD3 (HIT3a) AF700	Biolegend	cat # 300324; RRID: AB_493739
Anti-Human CD3 (OKT3) BV605	Biolegend	cat # 317322; RRID: AB_2561911
Anti-Human CD3 (SK7) PerCp-Cy5.5	Biolegend	cat # 344808; RRID: AB_10640736
Anti-Human CD38 (HIT2) APC	Biolegend	cat # 303510; RRID: AB_314362
Anti-Human CD38 (HIT2) FITC	Biolegend	cat # 303504; RRID: AB_314356
Anti-Human CD38 (HIT2) PE-Dazzle594	Biolegend	cat # 303538; RRID: AB_2564105
Anti-Human CD4 (OKT4) BV650	Biolegend	cat # 317436; RRID: AB_2563050
Anti-Human CD4 (OKT4) FITC	Biolegend	cat # 317408; RRID: AB_571951
Anti-Human CD4 (OKT4) PE-Cy5	Biolegend	cat # 317412; RRID; AB_571957
Anti-Human CD45 (HI30) AF700	Biolegend	cat # 304024; RRID: AB_493761
Anti-Human CD45RA (HI100) BV785	Biolegend	cat # 304140; RRID: AB_2563816
Anti-Human CD56 (5.1H11) PerCP-Cy5.5	Biolegend	cat # 362506; RRID: AB_2563914
Anti-Human CD8 (SK1) FITC	Biolegend	cat # 344704; RRID: AB_1877178
Anti-Human CD8 (RPA-T8) PerCP-Cy5.5	Biolegend	cat # 301032; RRID: AB_893422
Anti-Human CXCR3 (G025H7) BV711	Biolegend	cat # 353732; RRID: AB_2563533
Anti-Human CXCR5 (J252D4) FITC	Biolegend	cat # 356914; RRID:AB_2561896
Anti-Human CXCR5 (J252D4) PE	Biolegend	cat # 356904; RRID: AB_2561813
Anti-Human CXCR5 (J252D4) PE-Cy7	Biolegend	cat # 356924; RRID: AB_2562355
Anti-Human HLA-DR (L243) Pac blue	Biolegend	cat # 307633; RRID: AB_1595444
Anti-Human IFN-g (4S.B3) PE-Cy7	Biolegend	cat # 502528; RRID: AB_2123323
Anti-Human IgD (IA6-2) APC-Cy7	Biolegend	cat # 348218; RRID: AB_11203722
Anti-Human IL-10 (JES3-9D7) PE-Dazzle594	Biolegend	cat # 501426; RRID: AB_2566744
Anti-Human IL-17A (BL168) AF700	Biolegend	cat # 512318; RRID: AB_2124868
Anti-Human IL-4 (MP4-25D2) FITC	Biolegend	cat # 500806; RRID: AB_315125
Anti-Human PD-1 (NAT105) APC	Biolegend	cat # 367406; RRID: AB_2566067
Anti-Human PD-1 (EH12.2H7) Pac Blue	Biolegend	cat # 329916; RRID: AB_2283437
Anti-Human PD1 (EH12.2H7) AF700	Biolegend	cat # 329952; RRID: AB_2566364
Streptavidin APC conjugate	Invitrogen	cat # 17-4317-82
Streptavidin PE conjugate	Invitrogen	cat # 12-4317-87
Anti-Human TCRgd (5A6.E9) PE	Invitrogen	cat # MHGD04; RRID: AB_10374518
Anti-Human TNF-a (MAb11) Pac-Blue	Biolegend	cat # 502920; RRID: AB_528965
TotalSeq C0071 Anti-Human CCR4 (L291H4)	Biolegend	cat # 359425; RRID: AB_2800988
TotalSeq C0088 Anti-Human PD-1 (EH12.2H7)	Biolegend	cat # 329963; RRID: AB_2800862
TotalSeq C0140 Anti-Human CXCR3 (G025H7)	Biolegend	cat # 353747; RRID: AB_2800949
TotalSeq C0144 Anti-Human CCR6 (G034E3)	Biolegend	cat # 353440; RRID: AB_2810563
TotalSeq C0144 Anti-Human CXCR5 (J252D4)	Biolegend	cat # 356939; RRID: AB_2800968
TotalSeq C0154 Anti-Human CD27 (O323)	Biolegend	cat # 302853; RRID: AB_2800747
TotalSeq C0159 Anti-Human HLA-DR (L243)	Biolegend	cat # 307663; RRID: AB_2800795
TotalSeq C0251 Anti-Human Hashtag 1 (LNH-94; 2M2)	Biolegend	cat # 394661; RRID: AB_2801031
TotalSeq C0252 Anti-Human Hashtag 2 (LNH-94; 2M2)	Biolegend	cat # 394663; RRID: AB_2801032
TotalSeq C0253 Anti-Human Hashtag 3 (LNH-94; 2M2)	Biolegend	cat # 394665; RRID: AB_2801033
TotalSeq C0254 Anti-Human Hashtag 4 (LNH-94; 2M2)	Biolegend	cat # 394667; RRID: AB_2801034
TotalSeq C0255 Anti-Human Hashtag 5 (LNH-94; 2M2)	Biolegend	cat # 394669; RRID: AB_2801035
TotalSeq C0256 Anti-Human Hashtag 6 (LNH-94; 2M2)	Biolegend	cat # 394671; RRID: AB_2820042
TotalSeq C0257 Anti-Human Hashtag 7 (LNH-94; 2M2)	Biolegend	cat # 394673; RRID: AB_2820043
TotalSeq C0258 Anti-Human Hashtag 8 (LNH-94; 2M2)	Biolegend	cat # 394675; RRID: AB_2820044
TotalSeq C0384 Anti-Human IgD (IA6-2)	Biolegend	cat # 348245; RRID: AB_2810553
TotalSeq C0389 Anti-Human CD38 (HIT2)	Biolegend	cat # 303543; RRID: AB_2800758
anti-human IgG Qdot 800 (Custom)	Invitrogen	cat # C47091; RRID: AB_10556783
horseradish peroxidase (HRP)-conjugated anti-mouse IgG	KPL	cat # 074-1802
anti-NP mAbs (Millipore Cat. Nos. MAB 8257 and MAB 8258	Millipore Sigma	cat # MAB8257F; RRID: AB_347730
Anti-Influenza A Antibody, nucleoprotein, clone A1	Millipore Sigma	cat # MAB8258; RRID: AB_95232
monoclonal influenza IgG antibody (clone CR9114)	Creative Biolabs	cat # PABX-199
Goat Anti-Human IgG+IgM+IgA H&L (HRP)	abcam	cat # ab102420; RRID: AB_10712551
Bacterial and virus strains
A/California/07/2009 H1N1 virus	Wagar Lab	N/A
A/California/07/09 xX A/Puerto Rrico/8/1934 reassortant H1N1 virus	BEI	cat # NR-44004
Biological samples
Healthy Human Tonsils	Universty of California, Irvine Medical Center	Table 1
Fetal Bovine Serum, heat inactivated	R&D Systems	cat # S11550
Bovine Serum Albumin (BSA)	Fisher Scientific	cat # BP9700100
Bovine Serum Albumin (BSA)	Millipore Sigma	cat # A9085
Chemicals, peptides, and recombinant proteins
Ham’s F12 medium	Gibco	cat # 31765035
Normocin	InvivoGen	cat # ant-nr-1
Penicillin-Streptomycin	Gibco	cat # 15140122
Antibiotic-Antimycotic	Gibco	cat # 15240096
Lymphoprep	Stemcell	cat # 7851
DMSO	Sigma	cat # D4540-100ML
RPMI1640 with glutamax	Gibco	cat # 61870036
Nonessential amino acids	Gibco	cat # 11140050
Sodium pyruvate	Gibco	cat # 11360-070
Insulin, selenium, transferrin supplement	Gibco	cat # 41400045
Recombinant human BAFF	Biolegend	cat # 559602
Influenza vaccine (LAIV FluMist® Quadrivalent) 2019-2020	medImmune	cat # NDC 66017-306-01
Influenza vaccine (IIV, Fluzone® Quadrivalent) 2019-2020	Sanofi Pasteur	cat # NDC 49281-419-88
PBS	Gibco	cat # 10010-023
Sodium azide	Thermo Fisher	cat # 71448-16
EDTA 0.5M, pH 8.0	Invitrogen	cat # 15-575-020
Sodium bicarbonate	Sigma	cat # S5761
Sodium carbonate	Sigma	cat # 223530
TPCK-treated trypsin	Worthington Biochemical	cat # NC9783694
Eagle's Minimum Essential Medium (EMEM)	ATCC	cat # 30-2003
Triton X-100	Thermo Scientific	cat # 85111
3,3′,5,5′-tetramethylbenzidine (TMB) peroxidase substrate (SureBlue)	Seracare	cat # 5120-007
Tween-20	Sigma	cat # P1379-250ML
Universal Type I IFN Protein	R and D Systems	cat # 11200-1
Hemagglutinin A/California/07/2009 (H1N1)	Immune Technology	cat # IT-003-SW12ΔTMp
Hemagglutinin A/Brisbane/02/2018 (H1N1)	Immune Technology	cat # IT-003-0011ΔTMp
Hemagglutinin A/Kansas/14/2017 (H3N2)	Immune Technology	cat # IT-003-00436p
Hemagglutinin B/Phuket/3073/2013	Immune Technology	cat # IT-003-B11ΔTMp
Hemagglutinin B/Colorado/06/2017	Immune Technology	cat # IT-003-B21▵TMP
Influenza A H1N1 (A/California/04/2009) Neuraminidase	Sino Biologicals	cat # 11058-V08B
Influenza A H1N1 (A/California/07/2009) Nucleoprotein / NP Protein	Sino Biologicals	cat # 40205-V08B
Critical commercial assays
Cyto-Fast Fix/Perm buffer	Biolegend	cat # 426803
Zombie Aqua™ Fixable Viability Kit	Biolegend	cat # 423101
EZ-link micro NHS-PEG4-biotinylation kit	Thermo Scientific	cat # 21955
immPACT AEC Substrate Kit, Peroxidase	Vector	cat # SK-4205
ProcartaPlex Human Cytokine/Chemokine Panel 1A 34 plex	Invitrogen	cat # EPX340-12167-901
Chromium Next GEM Single Cell 5’ Kit	10x Genomics	cat # 1000263
5’ Feature Barcode Kit	10x Genomics	cat # 1000256
Chromium Single Cell Human BCR Amplification Kit,	10x Genomics	cat # 1000253
Chromium Single Cell Human TCR Amplification Kit	10x Genomics	cat # 1000252
Chromium Next GEM Chip K Single Cell Kit	10x Genomics	cat # 1000286
Deposited data
Raw and analyzed data	This paper	NCBI SRA: PRJNA980687
Experimental models: Cell lines
Madin-Darby Canine Kidney (MDCK) cells	ATCC	cat # CCL-34
Software and algorithms
GraphPad Prism	GraphPad Software	Version 8.0
FlowJo	BD Bioscience	Version 10.8.1
Seurat	R Package	Version 4.3
Belysa software	Sigma	Version 1.2
Cell Ranger Single Cell Software	10x Genomics	Version 6.1.1
Metascape	metascape.org	Version 3.5
Immcantation toolbox	R/Python Package	Version 4.0
Vegan	R Package	Version 2.6.2
Immunarch	R Package	Version 0.7.0
SoftMax Pro Software	Molecular Devices	Version 7.1
Other
MultiScreen-IP Filter Plate, 0.45 μm (PVDF)	Millipore	cat # MAIPS4510
Costar Assay plate 96 well, high-binding	Corning	cat # 3361